Kenneth R. Phelps

D-lactic acidosis in a man with the short-bowel syndrome.

WE have recently studied a patient who had short-bowel syndrome that presented with peculiar neurologic manifestations and severe metabolic acidosis. The anion gap was increased, but the identity o...

Heparin-Induced Hyperkalemia: Report of a Case

A 77-year-old diabetic man with a creatinine clearance of 23--27 ml/min developed hyperkalemia while receiving heparin for peripheral arterial insufficiency. Discontinuation of this agent led to resolution of hyperkalemia as the plasma aldosterone concentration multiplied by sixfold. Renal insufficiency may have predisposed this patient to the development of hyperkalemia when heparin therapy suppressed aldosterone synthesis.

Case Report: Adult T-Cell Leukemia/Lymphoma Associated with Recurrent Strongyloides Hyperinfection

Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year-old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed.

Histochemical demonstration of iron but not aluminum in a case of dialysis-associated osteomalacia

A patient undergoing hemodialysis is described in whom osteomalacia developed despite protracted treatment with calcitriol. Appropriately stained biopsy sections exhibited iron at all marrow-osteoid interfaces and a small fraction of trabecular mineralization fronts. Aluminum, the metal usually associated with osteomalacia in patients undergoing hemodialysis, was not histochemically demonstrable, even though spectrophotometrically measured bone aluminum content was substantial. These observations suggest two interpretations: iron may have caused osteomalacia through effects on bone cells and at mineralization fronts; alternatively, aluminum may have caused osteomalacia while remaining histochemically undetectable. It is possible that both metals exerted toxic effects simultaneously.

Acidosis-induced osteomalacia: Metabolic studies and skeletal histomorphometry

The pathogenesis of osteomalacia was investigated in three patients with chronic metabolic acidosis. Serum levels of parathyroid hormone and vitamin D metabolites were measured, and bone biopsy specimens were analyzed after double tetracycline labeling. Parathyroid hormone concentrations were normal in patients 1 and 3 and slightly elevated in patient 2. Vitamin D metabolism was undisturbed. Static indicators of bone remodeling substantiated the diagnosis of osteomalacia in each case. In patient 1 fluorescent microscopy revealed no evidence of tetracycline uptake. In patients 2 and 3 active mineralization was evident at all osteoid seams, but because double labels were rare, the mineral apposition rate appears to have been substantially reduced in most bone-forming units. Our results indicate that acidosis-induced osteomalacia, unlike that due to vitamin D deficiency, may be associated with mineral deposition at every possible site. Nevertheless, like other causes of osteomalacia, metabolic acidosis prevents mineral apposition at a normal rate even if mineral deposition is ubiquitous. We suggest that titration of newly deposited phosphate causes the observed impairment of mineral apposition and ultimately leads to osteomalacia.

Case Report: Pneumomediastinum Complicating Pneumocystis Carinii Pneumonia in a Patient with AIDS

The destructive potential of Pneumocystis carinii infection in patients with AIDS has been amply documented. This report describes a homosexual man with P. carinii pneumonia (PCP) complicated by pneumatocoeles and pneumomediastinum. The pneumomediastinum almost completely resolved with successful antimicrobial therapy. Pneumomediastinum, like pneumothorax, should be anticipated in patients with AIDS and PCP.

METABOLIC AND SKELETAL EFFECTS OF LOW AND HIGH DOSES OF CALCIUM ACETATE IN PATIENTS WITH PRETERMINAL CHRONIC RENAL FAILURE

Background: Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. Methods: Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4–8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. Results: The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from –27.0 to –39.6% and from –5.0 to –20.3%, respectively. The BMD increased at L1, L3, and L4. Conclusion: Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure.

Phosphate homeostasis, parathyroid hormone, and fibroblast growth factor 23 in stages 3 and 4 chronic kidney disease.

AIMS Increased concentrations of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) often coincide with normal serum phosphorus ([P]s) in chronic kidney disease (CKD). We hypothesized that the phosphate concentration ([P]f) in the cortical distal nephron (CDN) determines [PTH] and [FGF23] in this circumstance. METHODS We studied 29 patients with CKD at 4 visits and 28 controls at 1 visit. Assuming GFR = creatinine clearance (Ccr), we examined the following regressions: [P]s on its determinants, EP/Ccr and TRP/Ccr (P excretion and reabsorption per volume of filtrate); [PTH] and [FGF23] on [P]s and EP/Ccr; and TRP/Ccr on [PTH] and [FGF23]. We assumed that EP/Ccr is proportional to [P]f in the CDN. RESULTS In controls, [P]s correlated with TRP/Ccr but not EP/Ccr. [PTH] and [FGF23] were unrelated to [P]s, EP/Ccr, and TRP/Ccr. In CKD, [P]s correlated with EP/Ccr and TRP/Ccr. [PTH] correlated with [P]s at 2 visits and with EP/Ccr at 4; [FGF23] correlated with [P]s and EP/Ccr at all visits. TRP/Ccr correlated with [FGF23] and [PTH] at one visit each. CONCLUSIONS [P]f in the CDN, not [P]s, determined [PTH] in CKD. Because [FGF23] was consistently associated with only one determinant of [P]s, EP/Ccr, we infer that [P]f also determined [FGF23]. In patients with CKD, we speculate that [P]f in the CDN regulates FGF23 synthesis at that site.

Tubular calcium reabsorption and other aspects of calcium homeostasis in primary and secondary hyperparathyroidism.

AIMS Primary hyperparathyroidism (PHPT) causes hypercalcemia by increasing tubular calcium reabsorption. Because chronic kidney disease (CKD) is associated with normocalcemia, we inferred that calcium reabsorption is also normal, and hypothesized that normal reabsorption requires excessive parathyroid hormone (PTH) in CKD. METHODS The following were obtained in controls and patients with CKD or PHPT: estimated GFR (eGFR); concentrations of PTH 1-84, 1,25-dihydroxyvitamin D, and ultrafilterable and ionized calcium ([PTH], [1,25(OH)2D], [Ca]uf, [Ca]i); and ratios of calcium excreted or reabsorbed per volume of filtrate (ECa/Ccr, TRCa/Ccr). Pertinent linear regressions were examined. RESULTS In CKD, [PTH] was increased, but ECa/Ccr, TRCa/Ccr, [Ca]uf, and [Ca]i equaled control values. [PTH] was inversely related to eGFR but unrelated to [1,25(OH)2D]. TRCa/Ccr was constant at all [PTH]. In PHPT, [PTH] was no higher than in CKD, but TRCa/Ccr, [Ca]uf, and [Ca]i were increased. [1,25(OH)2D] correlated with [PTH]. In controls, TRCa/Ccr varied directly with [1,25(OH)2D] and inversely with [PTH]. CONCLUSIONS In controls, calcium reabsorption rose with [1,25(OH)2D], and [PTH] fell in response. In PHPT, [PTH] determined [1,25(OH)2D]; together, the hormones increased calcium reabsorption and caused hypercalcemia. In CKD, normal calcium reabsorption required high [PTH].

Parameters of phosphorus homeostasis at normal and reduced GFR: theoretical considerations.

AIMS Influx and reabsorption of phosphorus (IP and TRP) are assessed with fractional excretion and reabsorption (FEP and FTRP, nl ≤ 20% and ≥ 80%), or with excretion and reabsorption per volume of filtrate (EP/GFR and TRP/GFR, fasting nl ≈ 0.4 and 3.0 mg/dL). We analyzed these parameters at normal and reduced GFR. METHODS We equated GFR with creatinine clearance (Ccr) to develop necessary equations. We plotted serum phosphorus ([P]s), EP/Ccr, and FEP against their determinants, and TRP/Ccr against EP/Ccr at FEP of 20% or 40%. RESULTS Linear equations related [P]s to EP/Ccr and TRP/Ccr, and EP/Ccr to [cr]s and [P]u/[cr]u (a surrogate for IP). FEP rose in curvilinear fashion as Esub>P/Ccr rose and TRP/Ccr fell; changes in low values of EP/Ccr and TRP/Ccr induced large changes in FEP. At increased EP/Ccr (as in CKD), maintenance of FEP ≤ 20% required impossibly high TRP/Ccr; at EP/Ccr of 2.0 mg/dL, FEP and FTRP of 40% and 60% required normal TRP/Ccr. CONCLUSIONS EP/Ccr varies with IP at normal GFR, and with IP and [cr]s at low GFR. FEP, a function of EP/Ccr and TRP/Ccr, varies primarily with the lower ratio, which is always EP/Ccr at normal GFR. At low GFR, high FEP is inevitable if IP is preserved, and TRP/Ccr may be normal despite low FTRP. Contributions of IP and TRP to [P]s should be assessed with EP/Ccr and TRP/Ccr. FEP and FTRP have limitations at any GFR.